Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

RNAi Therapy Reduces Huntington's Disease Symptoms in Mouse Model

By BiotechDaily International staff writers
Posted on 01 Jun 2014
A research team used advanced gene therapy techniques to block the production of huntingtin (Htt), the toxic protein found in the brains of patients suffering from the fatal, inherited neurodegenerative disorder, Huntington's disease (HD).

Huntington’s disease is caused by a dominant gene that encodes the huntingtin protein. The 5' end of the HD gene has a sequence of three DNA bases, cytosine-adenine-guanine (CAG), coding for the amino acid glutamine, that is repeated multiple times. Normal persons have a CAG repeat count of between seven and 35 repeats, while the mutated form of the gene has anywhere from 36 to 180 repeats. The mutant form of huntingtin is broken down into toxic peptides, which contribute to the pathology of the syndrome.

RNA interference (RNAi) therapy that seeks to selectively reduce the expression of Htt has emerged as a potential therapeutic strategy for this disorder. Investigators at the bio-therapeutics research company Genzyme (Framingham, MA, USA) have continued this approach by aiming to lower Htt levels and to correct the behavioral, biochemical, and neuropathological deficits shown to be associated with the YAC128 mouse model of Huntington's disease. To do this they treated these animals with a recombinant adeno-associated viral (AAV) vector that had been designed to deliver siRNA that targeted the degradation of the Htt transcript.

Results that support the continued development of AAV-mediated RNAi as a therapeutic strategy for HD were published in the May 21, 2014, issue of the journal Human Gene Therapy. They revealed that AAV-mediated RNAi was effective at transducing greater than 80% of the cells in the striatum and partially reducing the levels (by about 40%) of both wild-type and mutant Htt in this region. Concomitant with these reductions were significant improvements in behavioral deficits, reduction of striatal Htt aggregates, and partial correction of the aberrant striatal transcriptional profile observed in YAC128 mice.

Of particular importance was the finding that a partial reduction of both the mutant and wild-type Htt levels was not associated with any notable overt neurotoxicity.

Related Links:
Genzyme



Channels

Drug Discovery

view channel
Image: Researchers have attached two drugs—TRAIL and Dox—onto graphene strips. TRAIL is most effective when delivered to the external membrane of a cancer cell, while Dox is most effective when delivered to the nucleus, so the researchers designed the system to deliver the drugs sequentially, with each drug hitting a cancer cell where it will do the most damage (Photo courtesy of Dr. Zhen Gu, North Carolina State University).

Anticancer Drug Delivery System Utilizes Graphene Strip Transporters

The ongoing search by cancer researchers for targeted drug delivery systems has generated a novel approach that uses graphene strips to transport simultaneously the anticancer agents TRAIL (tumor necrosis... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Biotech Acquisition Designed to Accelerate the Development and Marketing of Immunosequencing Applications

Adaptive Biotechnologies Corp. (Seattle, WA, USA), a developer of next-generation sequencing (NGS) to profile T-cell and B-cell receptors, has acquired of Sequenta, Inc. (South San Francisco, CA, USA), which is expected to expedite and expand the use of innovative immunosequencing technology for researchers and clinicians... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.